The objectives of the proposed investigation is to obtain information on the mechanism of congenital brain abnormalities induced by environmental mercury. More specifically we are interested in investigating the following problems: 1) the role of brain Na,K-ATPase inhibition as a possible mechanism of methylmercury (MeHg)-induced CNS teratogenesis and behavioral abnormalities in newborn animals; 2) determine the minimal dose of MeHg which will induce neurotoxic abnormalities in newborn and mature animals; and 3) investigate by in vivo methods other sulfhydryl enzymes known to be inhibited by mercury to determine their role in fetal and adult neurotoxicity. Recent findings indicate that the major congenital malformation from methylmercury toxicity to pregnant mothers is neurological. Since it is known that the transport enzyme, Na,K-ATPase, is one of the most sensitive enzyme systems to mercury inhibition and is located on cellular membranes, it is readily susceptible to inhibition of ingested mercury. Also it is well established that inhibition of the transport enzyme will alter intracellular cation levels, cause disturbances in transport of essential substrates, alteration in carbohydrate metabolism, and disturbances in mitochondrial oxygen consumption. Thus, inhibition of Na,K-ATPase may alter intracellular synthetic and metabolic reactions to seriously affect embryogenesis and fetal development. Therefore, studies will be conducted to determine whether Hg administered to pregnant rats will cause inhibition of fetal brain Na,K-ATPase. A correlation will be attempted to determine whether enzyme inhibition precedes the development of congenital brain abnormalities.